Controlling growth of filamentous microorganisms

Abstract

PCT No. PCT/GB91/02234 Sec. 371 Date Oct. 12, 1994 Sec. 102(e) Date Oct. 12, 1994 PCT Filed Dec. 16, 1991 PCT Pub. No. WO93/12219 PCT Pub. Date Dec. 16, 1991A process for the cultivation in continuous culture of a filamentous microorganism in a culture medium to which are supplied sources of carbon and other appropriate nutrients. The carbon or another nutrient source is supplied in an amount limiting to the growth of the culture and constitutes a limiting nutrient thereto. The development of an unwanted variant of the filamentous microorganism is restricted or delayed by supplying a first nutrient source to the culture as a limiting nutrient, and thus changing the nutrient supply to the culture in a manner such that a second nutrient source replaces the first nutrient source as the limiting nutrient.

We claim: 
     
       1. A process for the cultivation in continuous culture of a filamentous microorganism in a culture medium to which are supplied sources of carbon and other nutrients, the carbon or another nutrient source being supplied in an amount limiting to the growth of the culture and constituting a limiting nutrient thereto wherein development of a variant of the filamentous microorganism is restricted or delayed by supplying a first nutrient source to the culture as a limiting nutrient and then changing the nutrient supply to the culture such that a second nutrient source replaces the first nutrient source as the limiting nutrient. 
     
     
       2. A process for the production of a proteinaceous product by cultivation in continuous culture of a filamentous microorganism in a culture medium to which are supplied sources of carbon and other nutrients the carbon or another nutrient source being supplied in an amount limiting to the growth of the culture and constituting a limiting nutrient thereto and separation of the filamentous microorganism from the culture wherein development of a variant of the filamentous microorganism is restricted or delayed by supplying a first nutrient source to the culture as a limiting nutrient and then changing the nutrient supply to the culture such that a second nutrient source replaces the first nutrient source as the limiting nutrient. 
     
     
       3. A process for the production of a metabolite by cultivation in continuous culture of a filamentous microorganism in a culture medium to which are supplied sources of carbon and other nutrients the carbon or another nutrient source being supplied in an amount limiting to the growth of the culture and constituting a limiting nutrient thereto and recovery of the metabolite from the filamentous microorganism produced or from the culture medium wherein development of a variant of the filamentous microorganism is restricted or delayed by supplying a first nutrient source to the culture as a limiting nutrient and then changing the nutrient supply to the culture such that a second nutrient source replaces the first nutrient source as the limiting nutrient. 
     
     
       4. A process as claimed in any preceding claim in which the filamentous microorganism is a strain of the genus Fusarium. 
     
     
       5. A process as claimed in any one of claims 1-3 in which after the second nutrient source is used, one or more further different nutrient sources are used in turn as the limiting nutrient. 
     
     
       6. A process according to claim 5 in which the nutrient sources are used as a limiting nutrient according to a regular cycle. 
     
     
       7. A process as claimed in claim 6 in which the replacement of nutrient sources as limiting nutrients is made at predetermined time intervals. 
     
     
       8. A process as claimed in any one of claims 1-3 in which the nutrient sources used as limiting nutrient are selected from carbon, magnesium, phosphate, sulphate and nitrogen. 
     
     
       9. A process as claimed in any one of claims 1-3 in which when a change in limiting nutrient is effected the dilution rate is decreased.